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Structural enzymology of Li(+)-sensitive/Mg(2+)-dependent phosphatases.

Patel S, Martínez-Ripoll M, Blundell TL, Albert A
J Mol Biol 320 1087-94 (2002)
Cited: 24 times
EuropePMC logo PMID: 12126627

Abstract

Li(+)-sensitive/Mg(2+)-dependent phosphatases have attracted considerable attention since they have been proposed as targets for lithium therapy in the treatment of manic-depressive patients. The members of this enzyme superfamily display low levels of sequence identity while possessing a common fold and active site. Extensive structural and biochemical data demonstrate the direct involvement of two metal ions in catalysis, and show that lithium exerts its inhibitory action by blocking the products at the active site. By exploiting the different inhibitory properties of magnesium and calcium, we have been able to solve the X-ray structures of the Li(+)-sensitive/Mg(2+)-dependent 3'-phosphoadenosine-5'-phosphatase in complex with its substrate and with its products. The structural comparison of these complexes provides a 3D picture of the different stages of the catalytic cycle. This gives new insights into the understanding of the biological function of this group of enzymes and their lithium inhibition, and should assist in the design of improved inhibitors of therapeutic value.

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  2. Review of lithium effects on brain and blood. Young W. Cell Transplant 18 951-975 (2009)
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  5. Strategies for Treatment-Resistant Depression: Lessons Learned from Animal Models. Réus GZ, de Moura AB, Borba LA, Abelaira HM, Quevedo J. Mol Neuropsychiatry 5 178-189 (2019)

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  2. The crystal structure of Pyrococcus furiosus UMP kinase provides insight into catalysis and regulation in microbial pyrimidine nucleotide biosynthesis. Marco-Marín C, Gil-Ortiz F, Rubio V. J Mol Biol 352 438-454 (2005)
  3. Structural and biochemical characterization of the type II fructose-1,6-bisphosphatase GlpX from Escherichia coli. Brown G, Singer A, Lunin VV, Proudfoot M, Skarina T, Flick R, Kochinyan S, Sanishvili R, Joachimiak A, Edwards AM, Savchenko A, Yakunin AF. J Biol Chem 284 3784-3792 (2009)
  4. Rv2131c from Mycobacterium tuberculosis is a CysQ 3'-phosphoadenosine-5'-phosphatase. Hatzios SK, Iavarone AT, Bertozzi CR. Biochemistry 47 5823-5831 (2008)
  5. Dissection of Escherichia coli glutamate 5-kinase: functional impact of the deletion of the PUA domain. Pérez-Arellano I, Rubio V, Cervera J. FEBS Lett 579 6903-6908 (2005)
  6. glpX gene of Mycobacterium tuberculosis: heterologous expression, purification, and enzymatic characterization of the encoded fructose 1,6-bisphosphatase II. Gutka HJ, Rukseree K, Wheeler PR, Franzblau SG, Movahedzadeh F. Appl Biochem Biotechnol 164 1376-1389 (2011)
  7. Structural and biochemical studies of TREX1 inhibition by metals. Identification of a new active histidine conserved in DEDDh exonucleases. Brucet M, Querol-Audí J, Bertlik K, Lloberas J, Fita I, Celada A. Protein Sci 17 2059-2069 (2008)
  8. Structure and activity of the metal-independent fructose-1,6-bisphosphatase YK23 from Saccharomyces cerevisiae. Kuznetsova E, Xu L, Singer A, Brown G, Dong A, Flick R, Cui H, Cuff M, Joachimiak A, Savchenko A, Yakunin AF. J Biol Chem 285 21049-21059 (2010)
  9. Structural elucidation of the binding site and mode of inhibition of Li(+) and Mg(2+) in inositol monophosphatase. Dutta A, Bhattacharyya S, Dutta D, Das AK. FEBS J 281 5309-5324 (2014)
  10. A lithium-sensitive and sodium-tolerant 3'-phosphoadenosine-5'-phosphatase encoded by halA from the cyanobacterium Arthrospira platensis is closely related to its counterparts from yeasts and plants. Zhang JY, Zou J, Bao Q, Chen WL, Wang L, Yang H, Zhang CC. Appl Environ Microbiol 72 245-251 (2006)
  11. Effects of Li+ transport and intracellular binding on Li+/Mg2+ competition in bovine chromaffin cells. Fonseca CP, Montezinho LP, Nabais C, Tomé AR, Freitas H, Geraldes CF, Castro MM. Biochim Biophys Acta 1691 79-90 (2004)
  12. Creation of salt-insensitive 3'(2'),5'-bisphosphate nucleotidase by modeling and mutagenesis approach. Aggarwal M, Kishan KV, Mondal AK. Arch Biochem Biophys 469 174-183 (2008)
  13. Functional Evolution of Proteins. Catazaro J, Caprez A, Swanson D, Powers R. Proteins 87 492-501 (2019)
  14. Mutagenesis of threonine to serine in the active site of Mycobacterium tuberculosis fructose-1,6-bisphosphatase (Class II) retains partial enzyme activity. Bondoc JMG, Wolf NM, Ndichuck M, Abad-Zapatero C, Movahedzadeh F. Biotechnol Rep (Amst) 15 48-54 (2017)
  15. Yeast 3',5'-bisphosphate nucleotidase: an affinity tag for protein purification. Yang Y, Ma J, Yang Y, Zhang X, Wang Y, Yang L, Sun M. Protein Expr Purif 97 81-87 (2014)
  16. Identification of a potential proton donor to the linking oxygen atom in a three-metal ion assisted catalysis pathway catalyzed by Fructose-1, 6-bisphosphatase. Wang J, Wang Z, Ling B, Cao N, Wang W. J Mol Graph Model 73 191-199 (2017)
  17. Role of aspartic acid residues D87 and D89 in APS kinase domain of human 3'-phosphoadenosine 5'-phosphosulfate synthase 1 and 2b: A commonality with phosphatases/kinases. Venkatachalam KV, Ettrich RH. Biochem Biophys Rep 28 101155 (2021)


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